Clinical Approaches to Correcting Vitamin D Inadequacy and Maintaining Adequacy (D2/D3)

Vitamin D is available in two forms, vitamin D2 and vitamin D3. It has previously been assumed that these two forms maintain blood vitamin D equally. However, this may not be the case. This study will evaluate whether D2 and D3 produce equal elevation of blood vitamin D. Additionally, it will evaluate whether once per month vitamin D dosing is as effective in maintaining blood vitamin D levels as daily dosing.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; Vitamin D Inadequacy
• Intervention / Treatment: Dietary supplement: Ergocalciferol (vitamin D2); Dietary supplement: Ergocalciferol (vitamin D2); Dietary supplement: Placebo; Dietary supplement: Cholecalciferol (vitamin D3); Dietary supplement: Cholecalciferol (vitamin D3)

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • UW Osteoporosis Clinical and Research Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Community dwelling men and women age ≥ 65 years.
2. Able and willing to sign informed consent.
3. Serum 25OHD concentration ≥ 10 and less than 60 ng/ml by HPLC.
4. Willing to avoid use of cod-liver oil and non-study vitamin D supplementation; standard multiple vitamins containing ≤ 400 IU used no more than once daily will be allowed

Exclusion Criteria:

1. Current hypercalcemia (serum calcium > 10.5 mg/dl) or untreated primary hyperparathyroidism.
2. History of nephrolithiasis.
3. Screening 25OHD concentration ≥ 60 ng/ml.
4. Baseline 24-hour urine calcium > 250 mg if female, > 300 mg if male.
5. Known risk factors for hypercalcemia, e.g., malignancy, tuberculosis, sarcoidosis, Paget's disease
6. History of any form of cancer within the past five years with the exception of adequately treated squamous cell or basal cell skin cancer.
7. Renal failure defined as a calculated creatinine clearance (Cockroft-Gault method) ≤ 25 ml/minute
8. Severe end-organ disease, e.g., cardiovascular, hepatic, hematologic, pulmonary, etc., which may limit ability to complete the study
9. Known malabsorption syndromes, e.g., celiac disease, radiation enteritis, active inflammatory bowel disease, etc.
10. Use of medications known to alter bone turnover including bisphosphonates, estrogen, selective estrogen receptor modulators, PTH, testosterone or calcitonin
11. Vitamin D intake greater than 5,000 IU daily
12. Treatment with any active metabolites of vitamin D within six months of screening
13. Treatment with any drug which may interfere with vitamin D metabolism, e.g., phenobarbital, phenytoin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Dietary supplement: Ergocalciferol (vitamin D2); oral capsule 50,000 IU once monthly for 12 months; Dietary supplement: Ergocalciferol (vitamin D2); oral capsule 1600 IU once daily for 12 months; Dietary supplement: Placebo; oral placebo capsule once daily for 12 months
Experimental: 2	Dietary supplement: Ergocalciferol (vitamin D2); oral capsule 50,000 IU once monthly for 12 months; Dietary supplement: Ergocalciferol (vitamin D2); oral capsule 1600 IU once daily for 12 months; Dietary supplement: Placebo; oral placebo capsule once daily for 12 months
Experimental: 3	Dietary supplement: Placebo; oral placebo capsule once daily for 12 months; Dietary supplement: Cholecalciferol (vitamin D3); 50,000 IU once monthly for 12 months; Dietary supplement: Cholecalciferol (vitamin D3); oral capsule 1600 IU once daily for 12 months
Experimental: 4	Dietary supplement: Placebo; oral placebo capsule once daily for 12 months; Dietary supplement: Cholecalciferol (vitamin D3); 50,000 IU once monthly for 12 months; Dietary supplement: Cholecalciferol (vitamin D3); oral capsule 1600 IU once daily for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome measure is change in 25OHD with various D2 and D3 dosing regimens.	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine whether once monthly vitamin D2 or D3 dosing is as effective as daily dosing in attainment, and subsequent maintenance, of 25OHD status	12 months
Delineate the effect of these vitamin D regimens on other parameters of skeletal relevance	12 months

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Neil Binkley, MD, University of Wisconsin - Institute on Aging

Publications and helpful links

General Publications

• Binkley N, Gemar D, Engelke J, Gangnon R, Ramamurthy R, Krueger D, Drezner MK. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab. 2011 Apr;96(4):981-8. doi: 10.1210/jc.2010-0015. Epub 2011 Feb 2.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: January 2, 2008
• First Submitted That Met QC Criteria: June 5, 2008
• First Posted (Estimate): June 6, 2008

Study Record Updates

• Last Update Posted (Estimate): October 5, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 2006-0013